This application is a request for funds to continue to support the training of graduate students in Cell and Developmental Biology at Harvard Medical School. Trainee support under this grant is primarily for first and second year students, but under unusual circumstances is used to support advanced students. These students are selected based on their potential for cell and developmental biology research. The program outlined in this proposal will support the graduate training of 23 Ph.D. students (about 13% of the enrolled first and second year students). Research activities in cell and developmental biology focuses on understanding the properties that enable cells of higher organisms to grow tissues and organs and the molecular processes that underlie the development of complex organisms. The program in Cell and Developmental Biology of Harvard Medical School is one of the major components of the Biological and Biomedical Sciences program (BBS). This is a transdepartmental graduate program with 299 graduate students and 230 faculty. Our student pool has improved markedly in their preparation and qualifications. Our faculty members are from the departments of Biological Chemistry and Molecular Pharmacology, Cell Biology, Genetics, Microbiology and Molecular Genetics, and Pathology at Harvard Medical School. The research activities of the program faculty on this training grant are concentrated in the following areas: development in metazoans and differentiation of cells (16 faculty), the cell cycle (14 faculty), cell death (3 faculty), signal transduction in developing systems (29 faculty), trafficking, the cytoskeleton, and cell asymmetry (15 faculty), proteolysis during the cell cycle and cell morphogenesis (3 faculty). The training program utilizes a multi-disciplinary approach based on class work, an extensive seminar and meeting program, and a vigorous research environment to educate students. Students admitted to the program have previous training in biology, biochemistry, molecular biology, genetics, microbiology, cell biology, or chemistry. This graduate research program leads to the awarding of a Doctorate of Philosophy. Students participate in both required and elective courses in the first and second years of training. Courses are selected in consultation with faculty preceptors who advise and direct students until they have their own advisory committees. Students in the program are required to take eight graduate courses and to conduct three rotations in different laboratories. Before starting their thesis work the students must acquire a strong background in biochemistry and cell biology and they must pass a qualifying examination in which they write and defend a research proposal.